BP1 and Nuclear Hormone Signaling in Breast Cancer

乳腺癌中的 BP1 和核激素信号传导

• 批准号: 7269395
• 负责人: JANICE L GABRILOVE
• 金额: $ 13.59万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-06-23 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7269395
• 关键词: Acute Myelocytic Leukemia; Anemia; Apoptosis; Biological; Blood Cells; Body part; Cancer Patient; Cell physiology; Characteristics; Chronic Lymphocytic Leukemia; Clinical; Clinical Research; Clinical Trials; Coagulation Process; Complex; Data; Defective spinal cord development; Development; Disease; Dysmyelopoietic Syndromes; Educational Curriculum; Erythrocytes; Erythropoiesis; Faculty; Funding; Growth; Growth Factor; Hematology; Hematopoiesis; Hormones; Infectious Agent; Lead; Life; Localized; Malignant Neoplasms; Manuscripts; Mentors; Mentorship; Midcareer Investigator Award in Patient-Oriented Research; Morbidity - disease rate; Myelosuppression; Nuclear; Numbers; Pancytopenia; Population; Preparation; Principal Investigator; Process; Production; Protocols documentation; Research Ethics Committees; Research Training; Signal Transduction; Stem cells; Stimulus; Therapeutic; Training Programs; United States National Institutes of Health; Welts; autocrine; base; career; cytokine; design; gene repression; genetic regulatory protein; malignant breast neoplasm; mortality; novel therapeutics; oncology; oxygen transport; programs

DESCRIPTION (provided by applicant): This is a "Midcareer Investigator Award in Patient-Oriented Research: PA-00-005" entitled Therapeutic Strategies in Disorders of Hematopoiesis. The formation of blood cells represents a complex interaction between stem cells, ceils making up the stromal microenvironment and growth regulatory proteins, which are presented in soluble and localized forms. These interactions give rise to an enormous number and diversity of cells that function in widely separated parts of the body to transport oxygen, defend against infectious agents and provide stimulus for clotting. Abnormalities that impair the process of blood cell development, such as Myelodysplasia and Acute Myelogenous Leukemia (AML); as well as Cancer, can lead to life threatening illness as welt as lineage specific myelosuppression or pancytopenia resulting in significant morbidity and mortality. This proposal focuses on the development, conduct and mentoring of scientifically based, hypothesis-driven pilot clinical investigations, designed to exploit inherent biological features of these specific diseases. Three distinct central hypotheses underlie the Candidate's present (currently funded) and new (to be supported by K24) clinical research efforts: 1) the therapeutic application of agents that interfere or reverse transcriptional repression will be of clinical utility in AML and MDS respectively; 2) inhibition of autocrine and microenvironmentally presented growth factors, which contribute to delays in programmed cell death, characteristic of disorders such as chronic lymphocytic leukemia (CLL), represents a novel therapeutic approach of potential utility; and 3) cytokines inhibitory for erythropoiesis contribute to anemia of cancer; strategies to overcome cytokine inhibition should augment red blood cell production in cancer patients and further reduce the clinical problem of anemia in this population. An important part of this application concerns the active mentorship of key junior faculty and hematology/oncology fellows who have chosen to pursue academic clinical research as a career path. This mentorship program consists of: 1) participation in specific curriculum in conjunction with the NIH funded Clinical Research Training Program (K30), for which the candidate serves as the Principal investigator, and IRB course on conduct in Clinical Research; 2) direct oversight, including weekly meetings for: (a) protocol and IND development; (b) accrual, data and regulatory review; (c) manuscript and presentation preparation.

描述（由申请人提供）：这是“以患者为导向的研究中的职业生涯中期研究者奖：PA-00-005”，标题为造血障碍的治疗策略。 血细胞的形成代表了干细胞、构成基质微环境的细胞和生长调节蛋白之间的复杂相互作用，这些蛋白以可溶性和局部形式存在。 这些相互作用产生了大量和多样性的细胞，这些细胞在身体广泛分离的部位发挥作用，以输送氧气、防御传染源并刺激凝血。 损害血细胞发育过程的异常，例如骨髓增生异常和急性髓性白血病（AML）；以及癌症，可导致危及生命的疾病以及谱系特异性骨髓抑制或全血细胞减少症，从而导致显着的发病率和死亡率。 该提案的重点是开发、实施和指导以科学为基础、假设驱动的试点临床研究，旨在利用这些特定疾病的固有生物学特征。 候选人当前（目前资助）和新的（将由 K24 支持）临床研究工作基于三个不同的中心假设：1）干扰或逆转录抑制药物的治疗应用将分别在 AML 和 MDS 中具有临床实用性； 2) 抑制自分泌和微环境中存在的生长因子，有助于延迟程序性细胞死亡，这是慢性淋巴细胞白血病（CLL）等疾病的特征，代表了一种具有潜在实用性的新型治疗方法； 3) 抑制红细胞生成的细胞因子导致癌症贫血；克服细胞因子抑制的策略应该增加癌症患者红细胞的产生，并进一步减少该人群贫血的临床问题。 该申请的一个重要部分涉及对选择从事学术临床研究作为职业道路的主要初级教师和血液学/肿瘤学研究员的积极指导。 该指导计划包括： 1) 参与与 NIH 资助的临床研究培训计划 (K30) 相关的特定课程，候选人担任该计划的首席研究员，以及 IRB 临床研究行为课程； 2) 直接监督，包括每周举行会议： (a) 方案和 IND 制定； (b) 应计、数据和监管审查； (c) 手稿和演示文稿的准备。

项目成果

Phase 2 trial of the histone deacetylase inhibitor romidepsin for the treatment of refractory multiple myeloma.

• DOI: 10.1002/cncr.25584
• 发表时间: 2011-01-15
• 期刊: CANCER
• 影响因子: 6.2
• 作者: Niesvizky, Ruben;Ely, Scott;Mark, Tomer;Aggarwal, Sangeeta;Gabrilove, Janice L.;Wright, John J.;Chen-Kiang, Selina;Sparano, Joseph A.
• 通讯作者: Sparano, Joseph A.